Our group has contributed to the identification and characterization of the role of oral lesions in HIV disease since the beginning of the epidemic. AIDS initially affected relatively affluent gay white adult men; subsequently, it crossed economic, sexual, ethnic, age, and gender boundaries. Our studies to date of the natural history of HIV disease have reflected his spread of the epidemic. They have included intravenous drug users, heterosexual populations, hemophiliacs, women, children, adolescents, and persons from minority groups. As the epidemic changes, most recently and notably because of therapeutic advances, it is important to chart the corresponding changes in the frequency and significance of HIV-related oral lesions. In Aim 1 we will examine the effects of use of highly active anti-retroviral therapy (HAART) on the prevalence and incidence of oral lesions in adolescent and adult men and women who primarily come from minority ethnic groups. We will examine the effect of HAART on the prognostic value of oral lesions for AIDS. In Aim 2 we will examine the association between failure of HAART and the prevalence of oral lesions. We will conduct these studies in a cohort of homeless persons and a cohort of adolescents, since non-compliance with HAART by members of both these groups places the wide population at high risk of treatment-resistance forms of HIV. In Aim 3 we will analyze the relationship between oral lesions and the specific immune response to the causative organisms off candidiasis, hairy leukoplakia, and oral warts, in relation to HAART use. We believe that our epidemiologic studies are unique with regard to the size and diversity of the cohorts available the quality of data available on the subjects, the extent and duration of the successful collegial interaction between the cohort investigators and our group, and the extraordinary level of cooperation and loyalty of the study subjects themselves. These characteristics focus our attention on research that can affect the prognosis of all HIV-infect persons.